Exocrine and endocrine modulation in common gastric carcinoma.

Diagnostic and prognostic implications of endocrine differentiation were evaluated in 103 common gastric adenocarcinomas and undifferentiated carcinomas. Maturely differentiated exocrine and endocrine phenotypes were evaluated by using gastric exocrine and endocrine markers along with intestinal exocrine and endocrine markers. Immunohistochemical analysis revealed that 66 tumors (64%) were positive for generic endocrine markers such as chromogranin A and/or synaptophysin. The 14 patients with more than 20% tumor cells positive for at least 1 endocrine marker experienced a poorer prognosis than patients with no (n = 37) or 1% to 20% (n = 52) positivity. The 16 carcinomas expressing the maturely differentiated exocrine gastric phenotype significantly correlated with poorer outcome compared with carcinomas with mature exocrine intestinal (n = 22) or mixed/gastrointestinal (n = 64) phenotypes. Among tumors expressing chromogranin A and/or synaptophysin, the maturely differentiated endocrine gastric phenotype (n = 26) was a negative prognostic factor compared with mature endocrine intestinal (n = 21) and mixed/gastrointestinal (n = 5) phenotypes. Endocrine differentiation and maturely exocrine/endocrine gastric phenotypes are associated with an unfavorable prognosis and may identify subsets of patients for tailored therapy.

Long-term outcome of patients with complete pathologic response after neoadjuvant chemoradiation for cT3 rectal cancer: implications for local excision surgical strategies.

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) followed by radical surgery including total mesorectal excision (TME) is standard treatment in patients with locally advanced rectal cancer. Emerging data indicate that patients with complete pathologic response (ypCR) after CRT have favorable outcome, suggesting the possibility of less invasive surgical treatment. We analyzed long-term outcome of cT3 rectal cancer treated by neoadjuvant CRT in relation to ypCR and type of surgery. METHODS: The study population comprised 139 patients (93 men, 46 women; median age 62 years) with cT3N0-1M0 mid and distal rectal adenocarcinoma treated by CRT and surgery (110 TME and 29 local excision) at our institution between 1996 and 2008. At pathology, ypCR was defined as no residual cancer cells in the primary tumor. RESULTS: Tumors of 42 patients (30.2%) were classified as ypCR. After a median follow-up of 55.4 months, comparing patients with ypCR to patients with no ypCR, 5-year disease-specific survival was 95.8% versus 78.0% (P = 0.004), and 5-year disease-free survival was 90.1% vs. 64.0% (P = 0.004). In patients with ypCR, no statistically significant outcome difference was observed between TME and local excision. In patients treated by local excision, comparing patients with ypCR to patients with no ypCR, 5-year disease-free survival was 100% vs. 65.5% (P = 0.024), and 5-year local recurrence-free survival was 92.9% vs. 66.7% (P = 0.047). CONCLUSIONS: With retrospective analysis limitations, our data confirm favorable long-term outcome of cT3 rectal cancer with ypCR after CRT and warrant clinical trials exploring local excision surgical strategies.

MUC gene abnormalities in sporadic and hereditary mucinous colon cancers with microsatellite instability.

Aim of this study was verifying whether mucin producing colon cancers (CRCs) could develop through a molecular pathway involving microsatellite instability (MSI) and MUC gene alterations. Out of 49 CRCs expressing variable amounts of mucin, 22 (44.9%) were MSI-H and 5 (10.2%) were MSI-L. MUC genes were analyzed by Southern blotting and extra bands were evident in the Variable Number Tandem Repetition (VNTR) regions of MUC2 (5 cases) and MUC5AC (2 cases), but not MUC1 and MUC4 genes. Since the somatic VNTR abnormalities were detected in 6 MSI-H and in 1 MSI-L tumors, they seem to be peculiar of mismatch repair defective CRCs. Our finding suggests that alteration and/or loss of structurally normal MUC genes may be an important step in the neoplastic molecular pathway of a subset of CRCs and that mutations involving VNTR repetitive sequences may exist in MSI tumors as a direct and/or indirect consequence of an inefficient MMR system.

Neoadjuvant therapy of rectal cancer new treatment perspectives.

During the past two decades, significant advances have been made in the management of patients with rectal cancer. A number of clinical studies have demonstrated the efficacy of preoperative chemoradiation therapy with 5-fluorouracil (5-FU)-based regimens in decreasing local recurrences and improving survival and the likelihood of sphincter preservation. Although 5-FU has been the standard drug used in combination with radiation therapy for many years, new effective drugs including capecitabine, raltitrexed, irinotecan and oxaliplatin have been recently investigated in combination with radiation therapy in the preoperative setting. In addition, novel targeted biological agents including epidermal growth factor receptor inhibitors and vascular endothelial growth factor inhibitors have been shown to enhance the antitumor effect of both radiation and chemotherapy and are currently being explored in initial clinical trials. In the present review we summarize the results of adjuvant therapy. In addition, we will discuss the recently reported phase I-II trials with new drug plus radiation combinations in the preoperative treatment of patients with rectal cancer.

Early gastric cancer: a single-institution experience on 60 cases.

AIMS AND BACKGROUND: The 5-year survival rate of early gastric cancer (EGC) is 85-100% after "curative" resection, as compared to 20-30% in advanced gastric cancer (AGC). Because of this relatively high cure rate, the interest in the diagnosis and therapy of EGC has been steadily increasing. The present study, based on 60 EGCs, in a single-institution, is aimed at critical evaluating the diagnostic procedures and surgical options. METHODS AND RESULTS: Sixty patients with early gastric cancer (36 men and 24 women; median age, 61 years; range, 28-84) were diagnosed and operated on. They represented 21% of all patients with gastric cancer (281) treated in the period January 1987 to December 2001. The most frequent symptom was epigastric pain (84%). Barium upper gastrointestinal radiography findings were strongly suggestive of malignancy in 56 cases (93%). Preoperative histopathological diagnosis of adenocarcinoma was performed in 57 cases (95%). In 3 cases (5%) severe epithelial dysplasia (associated with ulcer) was the first diagnosis, but the final diagnosis, on the basis of resected specimens, was well differentiated adenocarcinoma. The primary surgical procedure included: a) subtotal distal resection (49 cases); b) total gastrectomy (6) for proximal neoplastic extension; c) proximal gastric resection (2) for cardial cancer; d) degastro-total gastrectomy (3) for cancer of the stump. Two patients, previously treated with conservative surgery, underwent degastro-total gastrectomy for neoplastic microfocal extension to the resection margin and for early anastomotic recurrence, respectively. Mural infiltration was limited to the mucosa and submucosa in 36 and 24 cases, respectively. Lymph node metastases were found in 3 mucosal and 9 submucosal tumor cases, involving either the first and second echelon. No operative deaths or postsurgical complications occurred in this series. In the follow-up period (median, 63 months; range, 3-178) 7 patients died due to other causes; 1 developed liver metastases, another developed oropharyngeal cancer and 2 died of biopsy-proven lung cancer without evidence of recurrent or metastatic gastric cancer. CONCLUSIONS: The clinical presentation of EGC is aspecific. Preoperative endoscopy with multiple biopsies remains the most sensitive diagnostic procedure. For treatment, subtotal distal gastric resection with lymphadenectomy is the gold standard, but in some instances total gastrectomy may be indicated. Accurate pathological examination establishes the depth of infiltration, as well as the superficial extension of tumors and lymph node status. Although the prognosis of EGC is favorable, a medium-term follow-up should be planned.